A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated Bulky Stage II or Stage III or IV, Low-Grade B-Cell NHL.

Introduction: The decision to treat indolent B-cell NHL is often based on progressing bulky disease, worsening symptoms, and increasing hematologic derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with pentostatin (P), purine analog, cyclophosphamide (C), alkylator, and rituximab (R), anti-CD20 monoclonal antibody, represents a promising new approach in the treatment of patients with low grade NHL. Most regimens have utilized fludarabine as the purine analog, but the myelosuppression and immunosuppression of these combinations frequently results in severe infections. We have previously reported our experience with pentostatin and rituximab in a cohort of 133 previously treated and untreated patients with Grade III/IV NHL or CLL (2005 Pan-Pacific Lymphoma Conference).

Methods: Fifty-five patients have been enrolled in this study with an expected accrual of 100. Patients are being enrolled through the Pharmatech Research Network. Eligibility criteria allows previously treated and treatment naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification). Treatment consisted of intravenous infusions of P (4 mg/m²), C (600 mg/m²), and R (375 mg/m²) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after even-numbered cycles. Patients were stratified by disease and by prior treatment status.

Results: Forty-seven patients have been eligible for evaluation. NHL patients (median age 64, range 30–84) received a total of 236 cycles (median 6). The ECOG status was 0 (65%) and 1 (33%). The overall objective response rate was 70% (CR 21%, Cru 13%, PR 36%). There were 3 grade 4 neutropenias documented and there was a single grade 4 leukopenia. There were a total of 3 deaths all of which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in a 81 year-old female (PR) due to CHF and the last death, due to CAD, occurred in an 84 year-old woman (SD).

Conclusions: This immunochemotherapeutic regimen is very active in indolent Grade III/IV NHL and the incidence of significant toxities was extremely low. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. The use of combination therapy in elderly patients should be used with caution due to associated co-morbidities.